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Lightning Strikes Twice: Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations


Howell, N and Miller, AR and Mackey, DA and Arnold, A and Herrnstadt, C and Williams, IM and Kubacka, I, Lightning Strikes Twice: Leber Hereditary Optic Neuropathy Families with Two Pathogenic mtDNA Mutations, Journal of Neuro-Ophthalmology, 22, (4) pp. 262-269. ISSN 1070-8022 (2002) [Refereed Article]

DOI: doi:10.1097/00041327-200212000-00002


Objective: To report the clinical and mitochondrial genetic analyses of two families, each of which carries both the 11778 and 14484 Leber hereditary optic neuropathy (LHON) mutations in mitochondrial DNA. Methods: In addition to detailed clinical histories, the complete sequence of the mitochondrial DNA (mtDNA) from each family was determined. Results: A small Australian LHON family (Vic20) and a family from the United States carry the 11778 and 14484 LHON mutations. In addition to the optic neuropathy, one branch of the Baltimore LHON pedigree had a high incidence of a fatal infantile encephalopathy. In both families, the 14484 LHON mutation was homoplasmic, whereas the 11778 LHON mutation was heteroplasmic. Conclusions: There are no additional mtDNA sequence changes that explain the encephalopathy in the Baltimore LHON family, and a nuclear gene involvement is an alternative explanation that is supported by the available data. The ophthalmological characteristics and penetrance in the 11778 and 14484 "two-mutation" LHON families are not markedly more severe than those of classic LHON families who carry a single mtDNA mutation.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:49037
Year Published:2002
Web of Science® Times Cited:27
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2011-11-08

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